Caspase-triggered nano-aggregation probes and methods of use

US9642922B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Jianghong Rao · Sunnyvale, US
• Deju Ye · Mountain View, US
• Adam Shuhendler · Palo Alto, US
• Frederick T. Chin · Ceres, US
• Jongho Jeon · Palo Alto, US
• Bin Shen · Mountain View, US

Key dates

• Filing date: Aug 20, 2014
• Grant date: May 9, 2017
• Expiry date: Nov 15, 2034

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2510/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.